PSEN1 p.Ser365=
c.1095C>T · VCV4847284
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00492%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -0.03, phastCons 1 |
| Overall | ||
| CADD | 8.998 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00492%
European (non-Finnish) · 58/1,179,988 alleles
Filtering AF
0.00386%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00353%
Overall
0.00359%
58/1,613,804 alleles · very rare
exomes 54/1,461,862 · genomes 4/151,942 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PSEN1
- Protein
- p.Ser365=
- Coding
- c.1095C>T
- MANE Select
- NM_000021
- Type
- single nucleotide variant
- Location
- chr14:73211908 (GRCh38)
- Gene constraint
- LOEUF 0.425 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.27 · 27 PDB
- Residue 365
- a UniProt-annotated variant site (in ad3; uncertain significance); the 'required for interaction with ctnnb1' region; an α-helix
Similar variants
- PSEN1 p.Ser365Phe Uncertain significance ★ same residue
- PSEN1 c.869-1G>A Pathogenic/Likely pathogenic ★★ same type
- PSEN1 p.Ala231Thr Likely pathogenic ★★ same type
- PSEN1 p.Ala246Glu Pathogenic ★★ same type
- PSEN1 p.Ala285Val Pathogenic ★★ same type
- PSEN1 p.Ala426Pro Pathogenic/Likely pathogenic ★★ same type
- PSEN1 p.Ala431Glu Pathogenic ★★ same type
- PSEN1 p.Ala79Val Pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/psen1-p-ser365 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown